Hydrochloric Acid → N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide

HRID 1884232Notes

Reaction equation

HRID 1884232 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][NH:17][C:18](=[O:32])[C:19]([C:22]2[CH:31]=[CH:30][C:29]3[CH2:28][CH2:27][CH2:26][CH2:25][C:24]=3[CH:23]=2)=[CH:20][OH:21])=[CH:11][C:10]=1[O:33][CH3:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].Cl[CH:38]([F:40])[F:39].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.COCCOC>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][NH:17][C:18](=[O:32])[C:19]([C:22]2[CH:31]=[CH:30][C:29]3[CH2:28][CH2:27][CH2:26][CH2:25][C:24]=3[CH:23]=2)=[CH:20][O:21][CH:38]([F:40])[F:39])=[CH:11][C:10]=1[O:33][CH3:34])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6372ChlorodifluoromethaneHCID 14797Potassium HydroxideHCID 69901147N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide

Product 1

HCID 69900815N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

4.20 g (9.19 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 14.3 g (23.0 mmol) of 10% aqueous potassium hydroxide solution, 0.60 g (1.84 mmol) of tetrabutylammonium bromide and 40 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatography, 5% hydrochloric acid was added to the reaction mixture. The reaction mixture was extracted with ethyl acetate, washed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) and the obtained product was washed with hexane to give 2.4 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1281).

Workup

  1. customat room temperature
  2. additionwas added to the reaction mixture
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washwashed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. washthe obtained product was washed with hexane

Sources & evidence

ORD record
ord-209f025639714b65a4b7dc2922e80769
Source dataset
uspto-grants-2004_07
Patent number
US06762321B2

Reaction notes

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